Comprehensive analysis of the clinical manifestations and hematological parameters associated with secondary immune thrombocytopenia in patients with primary Sjögren syndrome: An observational study.

Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease that primarily affects exocrine glands and can lead to various extraglandular manifestations, including secondary immune thrombocytopenia (ITP). Understanding the clinical and hematological differences in pSS patients with and without secondary ITP is crucial for improved patient management and treatment strategies. This retrospective study, conducted from January 2020 to December 2023, involved a cohort of pSS patients, dividing them into 2 groups: those with secondary ITP and those without. Patients were evaluated using the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren Syndrome Patient-Reported Index (ESSPRI), Health Assessment Questionnaire, and other hematological parameters. Inclusion criteria were based on the American-European Consensus Group or ACR/EULAR classification criteria for pSS. Exclusion criteria included other autoimmune or hematological disorders, prior splenectomy, recent blood transfusions, and lack of informed consent. Statistical analysis was performed using SPSS software, with various tests applied to analyze the data, including logistic regression to identify risk factors for secondary ITP. Significant differences were noted in fatigue, lymphadenopathy, arthritis, mean age, and ESSDAI scores between the secondary ITP and non-secondary ITP groups. Patients with secondary ITP exhibited higher platelet counts, more prevalent lymphopenia, higher immunoglobulin G (IgG) levels, lower complement 3 levels, and reduced white blood cell and hemoglobin levels. Logistic regression analysis identified lymphadenopathy as a risk factor and arthritis as a protective factor for the development of secondary ITP. The study reveals distinct clinical and hematological characteristics in pSS patients with secondary ITP, suggesting a higher disease activity in this subset. These findings underscore the need for further exploration of these associations to develop more precise treatment approaches for pSS, focusing on preventing secondary ITP and improving patient outcomes.

Immune Thrombocytopenic Purpura (ITP) and Chorioretinopathy in Chronic Granulomatous Disease: A Case Report.

BACKGROUND: Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disorder characterized by impaired phagocytic function, leading to recurrent infections and granuloma formation. Genetic mutations in NADPH oxidase complex components, such as CYBB, NCF1, NCF2, and CYBA genes, contribute to the pathogenesis. This case report explores the possible ocular and hematologic complications associated with CGD. CASE PRESENTATION: A 6-year-old girl with a history of vitrectomy, membranotomy, and laser therapy due to congenital blindness (diagnosed with chorioretinopathy) was referred to the hospital with generalized ecchymosis and thrombocytopenia. Diagnostic workup initially suggested chronic immune thrombocytopenic purpura (ITP). Subsequent admissions revealed necrotic wounds, urinary tract infections, and recurrent thrombocytopenia. Suspecting immunodeficiency, tests for CGD, Nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) were performed. She had a low DHR (6.7), and her NBT test was negative (0.0%). Her whole exome sequencing results confirmed autosomal recessive CGD with a homozygous NCF1 mutation. CONCLUSION: This case underscores the diverse clinical manifestations of CGD, including recurrent thrombocytopenia and possible early-onset ocular involvement. The diagnostic challenges highlight the importance of a multidisciplinary approach involving hematologists, immunologists, and ophthalmologists for accurate diagnosis and management. The rare coexistence of ITP in CGD emphasizes the intricate link between immunodeficiency and autoimmunity, requiring tailored therapeutic strategies.

Acute primary CMV infection complicated by pneumonitis and ITP in young immunocompetent woman in a regional Queensland Hospital.

We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an immunocompetent patient. Treatment with oral valganciclovir for 2 weeks successfully led to complete clinical recovery. CMV is traditionally associated with infection in immunocompromised patients and neonates; however, evidence of severe CMV infections in immunocompetent hosts is emerging. It is important to highlight the broad range of clinical presentations of CMV infections to prevent diagnostic delay and associated morbidity and expense.

Distinguishing thrombotic thrombocytopenic purpura from primary immune thrombocytopenia accompanied by anemia using the carbon monoxide breath test.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological disorder. Early differentiation between TTP and primary immune thrombocytopenia (ITP) accompanied by anemia is crucial to initiate an appropriate therapeutic strategy. The objective of this study was to evaluate the predictive value of red blood cell lifespan (RBCLS), determined using the carbon monoxide breath test, in the differential diagnosis of these two diseases. METHODS: We conducted a retrospective analysis of 23 patients with TTP and 32 patients with ITP accompanied by anemia. RBCLS measurements were compared and evaluated between these two patient groups. RESULTS: TTP patients had a significantly shorter mean RBCLS (20 ± 8 days) than patients with ITP accompanied by anemia (77 ± 22 days, P < 0.001) and healthy controls (114 ± 25 days, P < 0.001). In TTP patients, RBCLS showed a significant negative correlation with reticulocyte percentage and lactic dehydrogenase levels (P < 0.001). When using a standard baseline of 75 days, RBCLS demonstrated a sensitivity of 100% and specificity of 53.1% in identifying TTP. The diagnostic accuracy could reach 93% by excluding the impact of gastrointestinal bleeding. By employing the Receiver Operator Characteristics (ROC) curve, the area under the curve for RBCLS was 0.985 (95% CI: 0-1, P < 0.01) in predicting TTP, with an optimal cut-off value of 32 days, and sensitivity and specificity of 95.7% and 96.9%, respectively. CONCLUSIONS: Our study proposes a simple and accessible method for evaluating RBCLS to differentiate between TTP and ITP accompanied by anemia.

Bleeding self-assessments by patients with immune thrombocytopenia (ITP): An agreement study.

We designed anagreement study to compare the results of bleeding assessments done in tandem by ITP patients and trained research staff. We used a modified version of the ITP Bleeding Scale, which captured the patients' worst bleeding event at any of nine anatomical sites since the time of the last assessment. Interrater agreement was determined using the 2-way kappa for the assessment of severe vs. non-severe bleeds. We analyzed 108 consecutive patients with ITP from the McMaster ITP Registry who had duplicate bleeding assessments. Two-way agreement was excellent for gynecological (k = 0.86, 95% CI 0.71-1.02), gastrointestinal (k = 1), genitourinary (k = 1), pulmonary (k = 1) and intracranial (k = 1) bleeds; good for skin (k = 0.68, 95% CI, 0.54-0.82), oral (k = 0.76, 95% CI, 0.53-0.98) and ocular (k = 0.66, 95% CI, 0.04-1-28) bleeds; and moderate for epistaxis (k = 0.58, 95% CI, 0.21-0.95). Bleeding self-assessments by ITP patients were similar to trained research staff, but disagreements in severity grades were more frequent with skin bleeds, oral bleeds and epistaxis. Bleeding self-assessments could simplify bleeding assessments in clinical trials.

How complicated can be a case with immune thrombocytopenic purpura?: postsplenectomy arterial thrombosis.

Arterial thrombus associated with the surgery can be seen in postsplenectomy cases, but there is no clear data in patients diagnosed with immune thrombocytopenic purpura (ITP). A 52-year-old female patient was admitted to the emergency department due to ecchymotic skin changes. Her initial platelet count was 6000/mm 3 ; after two courses of high dose-dexamethasone, intravenous immunoglobulin and rituximab, splenectomy was planned for the patient whose platelet count was again <40 000/mm 3 . She presented to the emergency department with complaints of pain and pallor in the right arm in the second week of follow-up. There was a mural thrombus that caused approximately 50% stenosis in the lumen at the division site in the aortic arch, proximal of the right subclavian artery. The patient's clinic was found to be associated with the presence of an aberrant right subclavian artery and postoperative thrombocytosis/inflammation after elimination other prothrombotic conditions.

Conspicuous Peripheral Retinal Hemorrhages with a Relatively Preserved Posterior Pole in Immune Thrombocytopenic Purpura.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a rare auto-antibody mediated disease of isolated thrombocytopenia (<100,000/µL) with normal haemoglobin levels and leukocyte counts. Only a small number of ITP cases have been reported with accompanying ophthalmological findings. Herein, we report an ITP case with demonstrative retinal haemorrhages. CASE PRESENTATION: A fifty-five-year-old woman with a known history of type 2 diabetes mellitus was referred to our clinic with blurred vision. After detailed anamnesis and clinical assessment, she was diagnosed as primary ITP in haematology department, and systemic steroid (1.5mg/kg) therapy was initiated. During her follow-up, a concomitant peripheral facial paralysis (PFP) emerged. In the course of follow-up, her platelet counts increased gradually, the retinal haemorrhages regressed partially, and the PFP recovered completely. CONCLUSION: ITP is a rare haematologic disease that sometimes manifests with additional systemic involvements, and this disease should be remembered in the differential diagnosis of unusual retinal haemorrhages, which might be the only presenting feature.

Is Immune Thrombocytopenia and its Treatment Associated with Sarcopenia?

BACKGROUND: Immune thrombocytopenia (ITP) is defined as an isolated platelet count less than 100 × 109/L in the absence of other causes of thrombocytopenia. Sarcopenia is a body-wide muscular disorder with a progressive nature that leads to reduced mobility, physical disability, falls, and poor quality of life. We aimed to evaluate the frequency of objectively diagnosed sarcopenia in patients with ITP and to determine whether ITP therapies have sarcopenic effects. METHODS: This prospective study included patients who were followed up with ITP in the hematology outpatient clinic. Patients who had received corticosteroids within 3 months were excluded. The handgrip strength test, appendicular skeletal muscle mass (ASMM), ASMM/height2 value, soft lean mass (SLM), trunk soft lean mass (SLMT), and the 6-min walking speed test were applied for muscular evaluations and physical performance assessment. RESULTS: We included 53 patients (female/male: 73.58%/26.42%). While sarcopenia was not observed in 77.36% of ITP patients, possible sarcopenia was diagnosed in 9.43% and confirmed sarcopenia in 13.21%. Severe sarcopenia was not seen in any of the patients. Loss of muscle strength was observed in 22.64% of patients. SLM was found to be low in 92.45%. CONCLUSION: Sarcopenia may be more frequent among patients with ITP compared to the population, and it is important to note that 92.45% of patients had low SLM and 54.72% had low SLMT. Eltrombopag therapy might be beneficial as demonstrated by higher SLM, ASMM, and ASMM/height2 values.

Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused by a cytokine storm involving interleukin-6 (IL-6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD-TAFRO); idiopathic plasmacytic lymphadenopathy (iMCD-IPL), involving thrombocytosis and hypergammaglobulinaemia; and iMCD-not otherwise specified (iMCD-NOS), which includes patients who do not meet criteria for the other subtypes. Disease pathogenesis is poorly understood, with potential involvement of infectious, clonal and/or autoimmune mechanisms. To better characterize iMCD clinicopathology and gain mechanistic insights into iMCD, we analysed complete blood counts, other clinical laboratory values and blood smear morphology among 63 iMCD patients grouped by clinical subtype. Patients with iMCD-TAFRO had large platelets, clinical severity associated with lower platelet counts and transfusion-resistant thrombocytopenia, similar to what is observed with immune-mediated destruction of platelets in immune thrombocytopenic purpura. Conversely, elevated platelet counts in iMCD-IPL were associated with elevated IL-6 and declined following anti-IL-6 therapy. Our data suggest that autoimmune mechanisms contribute to the thrombocytopenia in at least a portion of iMCD-TAFRO patients whereas IL-6 drives thrombocytosis in iMCD-IPL, and these mechanisms likely contribute to disease pathogenesis.

Immune thrombocytopenia (ITP) in pregnancy.

Immune thrombocytopenia (ITP) in pregnancy is challenging for both mother and fetus. Understanding the pathophysiology, treatments, and risks to the mother and fetus leads to proper management resulting in successful pregnancy and delivery in almost all cases.1 ITP in a pregnant woman has many similarities to ITP not in pregnancy although gestational thrombocytopenia can be confused with ITP. However, recognizing differences is instrumental in avoiding bleeding complications and toxicities of treatment. This Nutshell review focuses on the natural history of ITP in pregnancy, its treatment, and dilemmas.

Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis.

BACKGROUND: Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations. METHODS: Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability. DISCUSSION: Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting. SYSTEMATIC REVIEW REGISTRATION: CRD42020161206.

Sirolimus for the treatment of patients with refractory connective tissue disease-related thrombocytopenia: a pilot study.

OBJECTIVE: CTD-related immune thrombocytopenia (CTD-ITP) represents an unmet medical need because the drugs that are available are only partly effective and have considerable side-effects. The aim of this study was to assess the efficacy and safety of sirolimus in refractory CTD-ITP patients. METHODS: We did a single-arm, open-label, pilot study of sirolimus in patients with CTD-ITP unresponsive to, or intolerant of, conventional medications. Patients received oral sirolimus for 6 months at a starting dose of 0.5-1 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/ml. The primary efficacy end point was changes in platelet count, and overall response assessed according to the ITP International Working Group Criteria. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. RESULTS: Between November 2020 and February 2022, 12 consecutively hospitalized patients with refractory CTD-ITP were enrolled and prospectively followed. Of these, six patients (50%) achieved complete response, two (16.7%) achieved partial response, and four (33.3%) were no response under therapy. Three of four patients with primary Sjögren's syndrome and two of three patients with systemic lupus erythematosus achieved overall response. One of two patients with overlapping Sjögren's syndrome and systemic lupus erythematosus achieved complete response at 6 months. No severe drug-related toxicities were observed. CONCLUSION: Our results do support sirolimus as an alternative regimen for refractory CTD-ITP patients, including systemic lupus erythematosus and primary SS.

Risk-based and individualised management of bleeding and thrombotic events in adults with primary immune thrombocytopenia (ITP).

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20-30 × 109 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient- and disease-related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient-centric approach. Currently, evidence-based recommendations and validated tools are lacking to support decision-making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk-based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

How I diagnose and treat thrombocytopenia in geriatric patients.

ABSTRACT: Thrombocytopenia in older individuals is a common but diagnostically challenging condition that has variable clinical impact to those who are affected. Diagnostic approach requires evaluation of the preexisting clinical conditions, detailed review of medications, and assessment for disorders that warrant urgent treatment. In this article, we describe a systematic approach to diagnosis of thrombocytopenia and present a schematic review for management strategies. Three clinical scenarios are presented that are relevant for their prevalence and management challenges in an older adult population. The first scenario addresses primary immune thrombocytopenia (ITP) and reviews different treatment options. The second one addresses complications of thrombocytopenia in management of the myelodysplastic syndrome. The last one reviews diagnostic challenges of drug-induced ITP.

Risk of thrombocytopenia in neonates of thrombocytopenic mothers.

OBJECTIVE: Maternal thrombocytopenia during pregnancy may occur due to several possible etiologies, with potential neonatal impact. The aim of the present study was to investigate whether there is a correlation between maternal and neonatal platelet count among women with thrombocytopenia during pregnancy. METHODS: A cross-sectional retrospective study (2012-2019) was conducted at a tertiary medical center. Complete blood count was routinely measured in all patients on admission to the delivery ward. Thrombocytopenia was defined as a platelet count below 150 K/µL. Clinical and outcome parameters of thrombocytopenic mothers and their newborns were collected from the electronic files and analyzed by severity of maternal thrombocytopenia. RESULTS: Of 45 385 women with a documented platelet count at admission, 2841 (6.24%) had thrombocytopenia: 2623 (5.7%) mild (100-149 K/µL), 207 (0.45%) moderate (50-99 K/µL), and 11 (0.02%) severe (<50 K/µL). Eight newborns had thrombocytopenia; corresponding rates by severity of maternal thrombocytopenia were 0.11%, 1.43%, and 18.18% (P = 0.04). None of the thrombocytopenic neonates had an intraventricular hemorrhage or other bleeding complications. The correlation between maternal and neonatal platelet counts was weak (Pearson r = 0.038; P = 0.046). CONCLUSION: We suggest that although the chances of neonatal thrombocytopenia are higher with worsening maternal thrombocytopenia, actual occurrence is rare, and the correlation is poor. Therefore, maternal thrombocytopenia cannot be regarded as a significant risk factor for neonatal thrombocytopenia. Neonatal platelet count should be obtained when maternal thrombocytopenia is autoimmune or less than 100 K/µL.

Association Between Idiopathic Thrombocytopenic Purpura and Hemorrhagic and Nonhemorrhagic Stroke.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count. This may lead to an increased risk of hemorrhagic stroke but a lower rate of nonhemorrhagic stroke. The goal of this study was to evaluate the association between ITP and both hemorrhagic and nonhemorrhagic strokes using a large database. METHODS: We used the Nationwide Inpatient Sample (NIS) database to analyze the occurrence of hemorrhagic and nonhemorrhagic stroke in patients with and without a diagnosis of ITP from 2005 to 2014. RESULTS: Univariate analysis revealed a higher incidence of hemorrhagic stroke in patients with ITP in the year studied. (for example, in 2005: OR, 1.75; 95% CI, 1.57-1.94; P < 0.001; 2014: OR, 2.19; 95% CI, 2.03-2.36; P < 0.001). After adjusting for age, gender, race, and hypertension, hemorrhagic stroke remained significantly associated with ITP (in 2005: OR, 1.85; 95% CI, 1.49-1.89; P < 0.001; 2014: OR, 2.01; 95% CI, 1.86-2.18; P < 0.001) for all the years studied. Nonhemorrhagic stroke occurred at a lower rate in patients with ITP in most years (2006: OR, 0.91; 95% CI, 0.85-0.97; P = 0.004; 2014: OR, 0.88; 95% CI, 0.83-0.93; P < 0.001). Multivariate analysis confirmed a higher rate of nonhemorrhagic stroke in ITP patients. CONCLUSION: Our analysis showed that there was a higher rate of hemorrhagic stroke but a lower rate of ischemic stroke in ITP patients, suggesting an important role of platelets in the occurrence of stroke.